PROIECTUL DE CERCETARE EXPLORATORIE PN-III-P4-ID-PCE-2020-2269, “SCORUL DE RISC POLIGENIC DE PSIHOZE IN POPULATIA ROMANEASCA SI PARTICIPAREA LA STUDIUL GENETIC INTERNATIONAL PGC AL BOLII BIPOLARE (PRSBP-PGC)
“SCORUL DE RISC POLIGENIC DE PSIHOZE IN POPULATIA ROMANEASCA SI PARTICIPAREA LA STUDIUL GENETIC INTERNATIONAL PGC AL BOLII BIPOLARE (PRSBP-PGC)”
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Realizari in etapa a III-a
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PARTICIPARI LA MANIFESTARI STIINTIFICE INTERNE SI INTERNATIONALE
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Realizari in etapa a II-a
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PARTICIPARI LA MANIFESTARI STIINTIFICE INTERNE SI INTERNATIONALE
Finantator: UEFISCDI
Contract nr. 203/ 2021
Contractor: Spitalul Clinic de Psihiatrie “Prof. Dr. Alexandru Obregia”
Director proiect: Dr. Maria (Grigoroiu)-Serbanescu, cercetator stiintific gradul I in Compartimentul de Cercetare de Genetica Psihiatrica din Spitalul Obregia;
Membru titular al Academiei de Stiinte Medicale
Membri in echipa: Dr. Carmen Cristina Diaconu, cercetator stiintific gradul I (Institutul de Virusologie Stefan S. Nicolau); Dr. Ana Iulia Neagu, cercetator stiintific gradul III (Institutul de Virusologie Stefan S. Nicolau); Prof. dr. Dan Florin Mihailescu (Universitatea Bucuresti)
Pozitie doctorand ramasa libera in urma concursului din data de 6 aprilie 2021.
Pentru a ajunge la rezultate valide si cu aplicabilitate clinica in scopul elucidarii cauzelor genetice si al ameliorarii tratamentului farmacologic al pacientilor cu boala bipolara (boala maniaco-depresiva), boala care afecteaza 1%-2% din populatia oricarei tari, cercetarea de genetica psihiatrica actuala necesita esantioane de zeci de mii de pacienti si martori de control. Aceasta dimensiune a esantioanelor este impusa de cerintele de semnificatie statistica ale strategiei actuale de studiu genome-wide (GWAS), de poligenia fenotipurilor complexe si de eterogenitatea genetica a populatiilor (vezi publicatiile noastre anterioare in Nature Genetics (2019) , Cell (2018), Science (2018)). De aceea proiectul nostru este integrat in doua consortii internationale: PGC (Psychiatric Genomics Consortium) si ConLiGen (Consortium of Lithium Genetics).
Obiectivele proiectului se incadreaza in doua directii de cercetare:
- Genetica moleculara pentru descoperirea de mecanisme genetice si tratamente noi ale bolii bipolare in colaborare cu doua consortia internationale.
- Utilizarea metodei scorului de risc poligenic derivat din scanarea de genom pentru predictia riscului fenotipic in scopul testarii potentialei sale aplicatii clinice.
I. Genetica moleculara pentru descoperirea de mecanisme genetice si tratamente noi ale bolii bipolare in colaborare cu consortii internationale.
1) Descoperirea de gene noi si replicarea genelor gasite anterior semnificativ asociate cu boala bipolara in esantioane mari de origine europeana cu scopul de a detecta noi tinte farmacologice si gene cauzale cu potential de predictie a riscului fenotipic. De asemenea genele anterior descoperite si publicate in articole cu cateva mii de citari la care grupul nostru a participat (Stahl et al., Nature Genetics, 2019; Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium, Cell, 2018; Brainstorm Consortium, Science, 2018; Amare et al, Molecular Psychiatry , 2018)) vor fi examinate in privinta replicarii in noul esantion PGC, care include si un nou esantion romanesc de bolnavi bipolari si martori normali psihic recrutat in timpul desfasurarii prezentului proiect.
- Extinderea esantionului romanesc de bolnavi si martori . Deoarece aplicatiile clinice ale geneticii moleculare nu sunt posibile fara replicarea rezultatelor in esantioane independente PGC va incerca sa replice descoperirile anterioare intr-un esantion international nou de largi dimensiuni (de ordinal miilor de pacienti si martori normali ), care va include, pe langa pacienti si martori romani inca neinclusi in analize anterioare si noul esantion romanesc de 200 subiecti, care vor fi recrutati in acest proiect. Selectia pacientilor si a martorilor normali psihic se face in Spitalul Obregia cu ajutorul unor interviuri clinice de genetica psihiatrica , iar analiza moleculara se realizeaza in colaborare cu laboratroul de genetica al Institutului de Virusologie Stefan S Nicolau din Bucuresti si cu Institutul de Genetica Umana al Universitatii din Bonn, Germania.
- Continuarea investigatiei mecanismelor genetice implicate in raspunsul la tratamentul de intretinere cu saruri de litiu in boala bipolara prin detalierea relatiei dintre caracteristicile fenotipice ale bolii bipolare si mecanismele genetice ale raspunsului la tratament, deoarece este cunoscut faptul ca aproximativ 40% din pacienti raspund favorabil la tratamentul de intretinere cu litiu si administrarea sa indelungata poate avea efecte toxice. Noua directie de cercetare in cadrul Consortiului de Genomica a Litiului (ConLiGen) condus de Germania, in care Spitalul Obregia are unul din esantioanele cele mai mari si mai bine caracterizate fenotipic inclus si esantionul romanesc de pacienti bipolari tratati cel putin doi ani cu litiu o reprezinta rolul genelor din sistemul imunitar si al scorului polygenic pentru psihoze majore in raspunsul la tratament. Anterior grupul nostru a identificat pentru prima data cateva gene legate de raspunsul la tratamentul cu litiu in boala bipolara ((Hou et al, Lancet, 2016) .
II. Utilizarea metodei scorului de risc poligenic pentru predictia riscului de boala si a trasaturilor fenotipice cu potentiala aplicatie clinica.
Studiile de asociere genome-wide (GWAS) ale ultimilor ani pe esantioane multinationale foarte mari de pacienti cu psihoze majore (schizofrenie si boala bipolara) au generat seturi de SNP care ar putea avea aplicatie in practica clinica pentru predictia raspunsului la tratament si a riscului de boala. Dar datorita eterogenitatii genetice a populatiilor, a poligeniei fenotipurilor complexe cum sunt bolile psihice si a tehnicii imputarii SNP-urilor negenotipate in GWAS , seturile de SNP descoperite in esantioane multinationale trebuiesc testate in fiecare populatie specifica in esantioane independente de esantionul de descoperire pentru o eventuala utilizare clinica. Dupa cum remarca Peterson et al. (2019) si Wendt et al. ( 2020) “poligenia unei boli intr-o populatie poate sa nu reflecte poligenia aceleiasi boli intr-o alta populatie.” O ilustratie a acestei observatii este studiul nostru din 2020 (Grigoroiu-Serbanescu et al., Journal of Affective Disorders, 2020) care a testat cel mai recent set de SNP asociate cu ADHD (Demontis et al, 2019) intr-un esantion romanesc si un esantion englez de pacienti bipolari cu ADHD in copilarie. Acest set de SNP nu a putut diferentia pacientii bipolari cu ADHD in copilarie de martorii normali nici in esantionul romanesc, nici in esantionul englez, desi ADHD este recunoscut ca precursor al bolii bipolare la foarte multi pacienti.
In aceasta a doua directie de cercetare se incadreaza urmatoarele obiective ale proiectului:
4. Testarea intr-un esantion romanesc (RO) si intr-un esantion englez (UK) a valorii predictive a scorului de risc poligenic pentru schizofrenie PGC-SCZ-SNP-set 2020 (inca nepublicat) pentru a vedea daca acest set diferentiaza bolnavii de martori normali si daca poate prezice unele trasaturi fenotipice ale bolii bipolare (prezenta simptomelor psihotice congruente si incongruente, varsta de debut a bolii, prezenta istoriei familiale de psihoze majore). Acest obiectiv se realizeaza in colaborare cu departamentul de Psihiatrie Moleculara al University College London (UCL) si Suny State University, New York.
Investigarea scorului de risc poligenic pentru schizofrenie in boala bipolara-I se bazeaza pe suprapunerea genetica de aproximativ 85% a celor doua boli si pe suprapunerea simptomatologie clinice.
Scorul de risc poligenic pentru schizofrenie influenteaza si raspunsul la tratamentul cu litiu, dupa cum a demonstrat grupul nostru ConLiGen (Amare et al, JAMA Psychiatry, 2018)
5. Investigarea asocieri intre potentiale clustere de SNP semnificative pentru schizofrenia si unele trasaturi fenotipice ale bolii bipolare in esantionul romanesc extins (include pacienti si martori recrutati in proiecte anterioare si pacienti si martori recrutati in proiectul actual) pornind de la rezultate anterioare, in care noi am aratat asocierea unor gene descoperite in studii genome-wide multinationale (EGFR; AS3MT) in special cu varsta de debut a bolii bipolare (Grigoroiu-Serbanescu et al, Psychiatry Research, 2015).
6) Analiza valorii predictive a scorului de risc poligenic derivat din setul de SNP pentru boala bipolara PGC-BP-wave2 (2019) pentru unele subfenotipuri de boala bipolara ( prezenta simptomelor psihotice congruente si incongruente, polaritatea la debut, istoria familiala de psihoze majore).
Publicatii in cursul proiectului
2021
1) Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology .
Nature Genetics, 2021; 53(6):817-829. Factor de impact (IF) = 38,38; WOS :000651382200001
Autori: Mullins N, Forstner AJ, O'Connell KS, Coombes B, Coleman JRI, Qiao Z, Als TD, Bigdeli TB, Børte S, Bryois J, Charney AW, Drange OK, ……, Backlund L, Baune BT, Bellivier F, Bengesser S, Berrettini WH, Blackwood DHR, Boehnke M, Børglum AD, Breen G, Carr VJ, ………….Fullerton JM, Gawlik M, Gershon ES, Goes FS, Green MJ, Grigoroiu-Serbanescu M, Hauser J, Henskens F, Hillert J, Hong KS, Hougaard DM, Hultman CM, Hveem K, Iwata N, Jablensky AV, Jones I, Jones LA, Kahn RS, Kelsoe JR, Kirov G, Landén M, Leboyer M, Lewis CM, …… Nurnberger JI, Cichon S, Edenberg HJ, Stahl EA, McQuillin A, Di Florio A, Ophoff RA, Andreassen OA.
2) Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.
Molecular Psychiatry. 2021; 26 (6):2457-2470. IF = 15,992; WOS: 000519671200001
Autori: Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Cearns M, Heilbronner U, Degenhardt F, Tekola-Ayele F, Hsu YH, Shekhtman T, Adli M, Akula N, Akiyama K, ……..Étain B, Jamain S, Falkai P, Forstner AJ, Frisen L, Frye MA, Fullerton JM, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jiménez E, Kahn JP, Kassem L, Kuo PH, Kato T, Kelsoe JR, ……….Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Maj M, Turecki G, Vieta E, Veeh J, Witt SH, Wright A, Zandi PP, Mitchell PB, Bauer M, Alda M, Rietschel M, McMahon FJ, Schulze TG, Baune BT.
3) Characterisation of age and polarity at onset in bipolar disorder.
British Journal of Psychiatry, 2021; 219; 6, 659-669; IF = 10,671; WOS:000723150400009
Autori: Kalman, JL; Olde Loohuis, LM; Vreeker, A; McQuillin, A; Stahl, EA; Ruderfer, D; Grigoroiu-Serbanescu, M; Panagiotaropoulou, G; Ripke, S; Bigdeli, TB; ……………….. Di Florio A, Smoller J, Biernacka JM, McMahon F, Alda M, Müller-Myhsok B, Koutsouleris N, Falkai P, Freimer N, Andlauer T, Schulze T, Ophoff R A.
4) Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients
Translational Psychiatry. 2021 ;11(1):606. IF = 7,989; doi: 10.1038/s41398-021-01702-2.
Autori: Schubert KO, Thalamuthu A, Amare AT, Frank J, Streit F, Adl M, Akula N, Akiyama K, Ardau R, Arias B, Aubry JM, Backlund L, Bhattacharjee AK, Bellivier F, Benabarre A, …………… Fullerton JM, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Heilbronner U, Herms S, Hoffmann P, Hou L, Hsu YH, Jamain S, Jiménez E, Kahn JP, Leboyer M, Leckband SG, Maj M;…………., Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Squassina A, Stamm T, Stopkova P, Tekola-Ayele F, Tortorella A, Turecki G, Veeh J, Vieta E, Witt SH, Roberts G, Zandi PP, Alda M, Bauer M, McMahon FJ, Mitchell PB, Schulze TG, Rietschel M, Baune BT.
5) Prediction of lithium response using genomic data.
Scientific Reports . 2021; 11(1): 1155. IF = 4,997; WOS:000621767100033
Autori; Stone W , Nunes A , Akiyama K, Akula N , Ardau R , Aubry J-M , Backlund L , Bauer M, Bellivier F , Cervantes P, Chen H-Ch, Chillotti C, Cruceanu C, Dayer A , Degenhardt F, Del Zompo M , Forstner AJ, Frye M , Fullerton JM , Grigoroiu-Serbanescu M, Grof P , Hashimoto R , Hou L, Jiménez E , Kato T, Kelsoe J, Kittel-Schneider S, Kuo P-H , Kusumi I, Lavebratt C , Manchia M , Martinsson M, Mattheisen M , McMahon FJ, Millischer V , Mitchell Ph B, Nöthen MM , O'Donovan C, Ozaki N , Pisanu C , Reif A, Rietschel M, Rouleau G, Rybakowski J, Schalling M, Schofield PR , Schulze TG , Severino G, Squassina A , Veeh J, Vieta E , Trappenberg T, Alda M.
6) HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
Scientific Reports. 2021, 11 (1):Article number 17823. IF= 4,997; WOS:000693895300003
Autori : Le Clerc S, Lombardi L, Baune BT, Amare AT, Schubert KO, Hou L, Clark SR, Papiol S, Cearns M, Heilbronner HC, ……………Chillotti C, Cichon S, Cruceanu C, Czerski PM, Dalkner N, Dayer A, Del Zompo M, DePaulo JR, Étain B, Jamain S, Falkai P, Forstner AJ, Frisen L, Frye MA, Fullerton JM, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Herms S, Hoffmann P, Jiménez E, Kahn JP, Kassem L, Kuo PH, Kato T, Kelsoe JR, Kittel-Schneider S, Ferensztajn-Rochowiak E, König B, Kusumi I, Laje G, Landén M, Lavebratt C, Leckband SG, Tortorella A, Manchia M, Martinsson L, McCarthy MJ, McElroy SL, Colom F, Millischer V, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nöthen MM, Novák T, O'Donovan C, ………………………….., Leboyer M, Tamouza R.
7) Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study, Complex Psychiatry (ISSN: 2673-3005 (Print)), 2021; 7, 3-4, p. 80-89. doi.org/10.1159/000519707. (Karger, Basel); Publication date: 18.11.2021 IF = 1,2
Autori: Coombes B.J,· Millischer V,· Batzler A, Larrabee B, · Hou L, · Papiol S, · Heilbronner U, Adli M, · Akiyama K, · Akula N, · Amare A.T., · Ardau R,· Arias B, …………Cruceanu C,· Czerski P,· Dalkner N, · Degenhardt F, Del Zompo M, · DePaulo J.R, · Étain B, · Falkai P, · Ferensztajn-Rochowiak E, Forstner A, · Frisen L,· Gard S, · Garnham J,· Goes F, · Grigoroiu-Serbanescu M, · Grof P, Hashimoto R, · Hauser J, · Herms S, · Hoffmann P, · Jamain S,· Jiménez E,· Kahn J.-P, · Kassem L.d · Kato T.S · Kelsoe J, · Kittel-Schneider S,· König B, · Kuo P, · Kusumi I,· Laje G,· Landén M, · Lavebratt C, · Leboyer M, · Leckband S, · Maj M, · ……….· Fullerton J,· Alda M, · Frye M,· Schulze T.G, · McMahon F.J , Biernacka J.M.
8) Genetic risk for psychiatric illness is associated with the number of hospitalizations of bipolar disorder patients . Journal of Affective Disorders. 2022 ; 296:532-540. IF = impact factor = 6,53; WOS:000729867200023
Autori: Kalman JL, Papiol S, Grigoroiu-Serbanescu M, Adorjan K, Anderson-Schmidt H, Brosch K, Budde M, Comes AL, Gade K, Forstner A, Grotegerd D, Hahn T, Heilbronner M, Heilbronner U, Heilmann-Heimbach S, Klöhn-Saghatolislam F, Kohshour MO, Meinert S, Meller T, ……………..Falkai P, Dannlowski U, Kircher T, Schulze TG, Andlauer TFM
9) Sex-Dependent Shared and Non-Shared Genetic Architecture, Across Mood and Psychotic Disorders. Biological Psychiatry, 2022 ; 91(1): 102-117. (IF = 13,38). WOS:000747756000015
Autori: Blokland G, Grove J, Chen Ch, Cotsapas C, Tobet S, Handa R, Schizophrenia Working Group of the PGC, St Clair D, Lencz T, Mowry B J,, Periyasamy S, Cairns M J , ………., L. Sirignano, S. Cichon, Grigoroiu-Serbanescu M, J. Hauser, J. Lissowska, F. Mayoral, B. Müller-Myhsok, B. Świątkowska, T. G. Schulze, M. M. Nöthen, M. Rietschel, J. Kelsoe, M. Leboyer, S. Jamain, B. Etain, F. Bellivier, J. B. Vincent, M. Alda, …………, J. W. Smoller, Jill M. Goldstein.
10) Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach . British Journal of Pscyhiatry, 2022, 220, 219–228. IF = 10,67; WOS:000762249500001,
Autori: Cearns M, Amare AT, Schubert KO, Thalamuthu A, Frank J, Streit F, Adli M, Akula N, Akiyama K, Ardau R, Arias B, Aubry JM, Backlund L, ………. Bhattacharjee AK, Forstner AJ, Frisen L, Frye M A, Fullerton JM, Gard S, Julie S Garnham, Fernando S Goes, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hauser J, Heilbronner U, Herms S, Hoffmann P, Hofmann A, Hou L, Yi-Hsiang Hsu, Jamain S, Jiménez E,………. Bauer M, McMahon FJ, Mitchell PB, Schulze TG, Rietschel M, Clark SR, Baune BT.
11) Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors. . Biological Psychiatry. 2022; 91(3):313-327; IF = 13,38, WOS:000746060000012.
Autori: Mullins N, Kang J, Campos AI, Coleman JRI, Edwards AC, Galfalvy H, Levey DF, Lori A, …………Johnson C, Kaplan AS, Kaye WH, Keel PK, Kennedy JL, Klump KL, Li D, Liao SC, , ……………..Forstner AJ, Frye M, Fullerton JM, Gatt JM, Gejman PV, Giegling I, Grabe HJ, Green MJ, Grevet EH, Grigoroiu-Serbanescu M, Gutierrez B, Guzman-Parra J, Hamilton SP, Hamshere ML, Hartmann A, Hauser J, Heilmann-Heimbach S, Hoffmann P, Ising M, Jones I, Jones LA, Jonsson L, Kahn RS, , ….McQuillin A, Medland SE, Mehta D, Melle I, Milaneschi Y, Mitchell PB, ……….Lewis CM, Mann JJ, Rentería ME, Smith DJ, Stahl EA, Stein MB, Streit F, Willour V, Ruderfer DM.
12) Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses. European Archives of Psychiatry and Clinical Neurosciences. 2022; 272(8):1611-1620 ; IF = 5,76; WOS:000753708400001
Autori: Kalman JL, Yoshida T, Andlauer TFM, Schulte EC, Adorjan K, Alda M, Ardau R, Aubry JM, Brosch K, Budde M, Chillotti C, Czerski PM, DePaulo RJ, Forstner A, Goes FS, Grigoroiu-Serbanescu M, Grof P, Grotegerd D, Hahn T, Heilbronner M, Hasler R, Heilbronner U, Heilmann-Heimbach S, Kapelski P, Kato T, Kohshour MO, Meinert S, ………..Falkai P, Dannlowski U, Kircher T, Schulze TG, Papiol S
13) GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. American Journal of Psychiatry. 2023;180(10):723-738. Impact factor = 17,70
Autori: Docherty AR, Mullins N, Ashley-Koch AE, Qin X, Coleman JRI, Shabalin A, Kang J, Murnyak B, Wendt F, Adams M, Campos AI, DiBlasi E, Fullerton JM, Kranzler HR,…….., Bass N, …….. Craddock N , Srdjan Djurovic S, Foo J, Forstner A, Frye M , Gatt J, Giegling I , Grabe H J Green M, Grevet E , Grigoroiu-Serbanescu M., Gutierrez B , Guzman-Parra J , Hamshere M , Hartmann A , Hauser J , Heilmann-Heimbach S, Hoffmann P,…………… Coon H , Jean C Beckham J, Kimbrel N, Ruderfer D..
14) Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. Molecular Psychiatry. 2023, 11 Jul. doi: 10.1038/s41380-023-02149-1. Online ahead of print. Impact factor = 13,437
Autori: Amare AT, Thalamuthu A, Schubert KO, Fullerton JM, Ahmed M, Hartmann S, Papiol S, Heilbronner U, Degenhardt F, Tekola-Ayele F, Hou L, Hsu YH, Shekhtman T, Adli M, Akula N, Akiyama K, Ardau R, Arias B, Aubry JM, ………Falkai P, Forstner AJ, Frisen L, Frye MA, Gard S, Garnham JS, Goes FS, Grigoroiu-Serbanescu M, Fallgatter AJ, Stegmaier S, ,….. McMahon F, , Schulze TG. Clark SR. Baune BT.
15) Lack of guidelines and translational knowledge is hindering the implementation of psychiatric genetic counseling and testing within Europe . A multi-professional survey study.
European Journal of Medical Genetics. 2023 Aug; 66(8):104805; IF = 4
Autori: Koido K, Malmgren CI, Pojskic L, Almos PZ, Bergen SE, Borg I, Božina N, Coviello DA, Degenhardt F, Ganoci L, Jensen UB, Durand-Lennad L, Laurent-Levinson C, McQuillin A, Navickas A, Pace NP, Paneque M, Rietschel M, Grigoroiu-Serbanescu M, Soller MJ, Suvisaari J, Utkus A, Van Assche E, Vissouze L, Zuckerman S, Chaumette B, Tammimies K.
16) Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study. Translational Psychiatry, 2023, impact factor =7,989) (in revizie)
Autori: Kelsoe J, Ou A, Rosenthal S, Adli M, Akiyama K, Akula N, Alda M, Amare AT, Ardau R, Arias B, Aubry JM, Backlund L, Banzato C, Bauer M, Baune B, Bellivier F, Benabarre A, Bengesser S, Abesh B, Biernacka J, Bui E, Cervantes P, Chen GB, Chen HC, Chillotti C, …………..Frye M, Fullerton J, Gard S, Garnham J, Goes F, Grigoroiu-Serbanescu M, Grof P, Gruber O, Hashimoto R, Hauser J, Heilbronner U, Herms S, Hoffmann P, Hofmann A, Hou L, ……………Schulze T, Schweizer B, Seemüller F, Witt S , Wray N , Wright A, Young T, Zandi P , Del Zompo M.
17) Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder. (Translational Psychiatry, 2023, impact factor = 7,989) (in revizie)
Autori: Herrera-Rivero M, Gutiérrez-Fragoso K, Thalamuthu A, Amare AT, Adli M, Akiyama K, Akula N, Ardau R, Arias B, Aubry JM, Backlund L, Bellivier F, Benabarre A, ……Etain B, Falkai P, Ferensztajn-Rochowiak E, Forstner AJ, Frank J, Frisen L, Frye M, Fullerton J, Gallo C, Gard S, Garnham J, Goes F, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hasler R, Hauser J, Heilbronner U, Herms S, Hoffmann P, Hou L, Hsu Y, Jamain S, Jiménez E, ……………..Shimoda K, Simhandl C, Zandi P, Alda M, Bauer M, McMahon F, Mitchell P, Rietschel M , Schulze T , Bernhard Baune.
18) Exploring the genetics of lithium response in bipolar disorders”, International Journal of Bipolar Disorders, 2023 (in evaluare) (impact factor = 4).
Autori: Herrera-Rivero M, Gutiérrez-Fragoso K, Thalamuthu A, Amare AT, Adli M, Akiyama K, Akula N, Ardau R, Arias B, Aubry JM, Backlund L, Bellivier F, Benabarre A…………….Gallo C, Gard S, Garnham J, Goes F, Grigoroiu-Serbanescu M, Grof P, Hashimoto R, Hasler R, Hauser J, Heilbronner U, Herms S, Hoffmann P, Hou L, Hsu Y, Jamain S, Jiménez E, ……..Schofield P, Schubert KO, Schulte E, Schweizer B, Severino G, Shekhtman T, Shilling P, Shimoda K, Simhandl C, Zandi P, Alda M, Bauer M, McMahon F, Mitchell P, Rietschel M , Schulze T , Bernhard Baune. “
19) Genetic diversity boosts gene discovery and insight in bipolar disorder, Nature, 2023, impact factor = 64, (in evaluare).
Autori: 253 autori inclusiv Maria Grigoroiu-Serbanescu
20) Schizophrenia polygenic risk scores, clinical variables and genetic pathways as predictors of phenotypic traits of bipolar I disorder. Journal of Affective Disorders, 2023 , (impact factor 6,53) (in evaluare) .
Autori: Grigoroiu-Serbanescu M, van der Veen T, Bigdeli T, Herms S, Diaconu CC, Neagu A I, Bass N , Forstner AJ , Nöthen MM, McQuillin A
21) “Fine-mapping genomic loci refines bipolar disorder risk genes” Nature Neuroscience, 2023, impact factor 25, (in evaluare)
Autori: Koromina M, Ravi A, Panagiotaropoulou G, Schilder B, Humphrey J, Braun A, Bidgeli T, Chatzinakos C, Coombes B, Kim J, Liu X, Terao C O.’Connell KSO, Adams M, Adolfsson R, Alda M, ………Fellendorf T, Ferentinos P., Forstner AJ, Forty L., Frye M., Fullerton J, Gawlik M, Gizer I R , Gordon-Smith K, Grigoroiu-Serbanescu M, Guzman-Parra J, Hahn T, Henskens F, Hillert J., Jablenski A, Jones I, Jones L, Jonsson L……………. McElroy S, McGregor NW, McIntosh A, McQuillin A, Michie P, Milanova V, Moutsatsou P., Mowry B., , Myers R, Müller-Myhsok B, Nenadić I, Nöthen M, O.’Donovan C, O.’Donovan M, Ophoff R, Owen M., Pantelis ………..Ripke S, Towfique R, Coleman J R, Mullins N.
PARTICIPARE LA ACTIVITATI PSYCHIATRIC GENOMICS CONSORTIUM (PGC)
Maria (Grigoroiu)-Serbanescu – membru al grupului de clinicieni al PGC Bipolar Working Group
PARTICIPARI LA MANIFESTARI STIINTIFICE INTERNE SI INTERNATIONALE
2021
- Participare la conferinta europeana “The state of Genetic Testng and Genetic Counselling in Psychiatry across Europe” (14-17 Martie 2021) la invitatia organizatorilor cu prezentarea “Current state of genetic counselling and testing in psychiatry in Eastern Europe”’. ( Maria Grigoroiu-Serbanescu).
Conferinta a fost organizata de proiectul european EnGaGe condus de Germania
- Participare la Conferinta Nationala de Psihiatrie , 14 -17 iulie 2021 cu cursul
“Validitatea si utilitatea clinica a scorului de risc polygenic pentru psihozele majore (- boala bipolara si schizofrenie) ” . Autor Maria Grigoroiu-Serbanescu, Spitalul Clinic de Psihiatrie “Prof. Dr. Alexandru Obregia”
- World Congress of Psychiatric Genetics, 11-15 octombrie, 2021 (online)
Participare in cadrul Bipolar Group of PGC la simpozionul “ Revealing the Genetic Architecture of Bipolar Disorder and Subtypes Provides Biological Insight” .
PARTICIPARI LA MANIFESTARI STIINTIFICE INTERNE SI INTERNATIONALE, 2022
1) Doi membri ai echipei au participat la Conferinta Nationala de Psihiatrie organizata la Cluj in perioada 12-15 iulie 2022 la invitatia prof. dr. Doina Cozman, presedinta Asociatiei Romane de Psihiatrie, de a organiza un simpozion de genetica psihiatrica pentru psihiatri clinicieni (vezi invitatia).
Directorul de proiect a organizat simpozionul “Arhitectura genetica a psihozelor majore (schizofrenie, boala bipolara, depresie majora unipolara)” si a prezentat lucrarea “Arhitectura genetica a psihozelor majore – status actual si perspective pentru practica clinica” . Dr. Carmen Diaconu a prezentat lucrarea “De la genomica la teste diagnostice in bolile psihiatrice: aplicarea informatiei furnizate de tehnologiile genomice in diagnosticul individual”.
- Directorul de proiect a participat la Congresul Mondial de Genetica Psihiatrica de la Florenta (12-18 septembrie 2022) cu lucrarea “Schizophrenia SNP-set wave3 (2022) predicts psychosis, age of onset and age of onset of first depressive episode in bipolar I disorder” , autori Maria Grigoroiu-Serbanescu, Tim Bigdeli, Stefan Herms, Carmen C Diaconu, Ana Iulia Neagu, Tracey van der Veen, Nick Bass, Dan Florin Mihailescu, Markus M. Nöthen , Andreas J Forstner , Andrew McQuillin.
Rezultate preliminare prezentate la Congresul Mondial de Genetica Psihiatrica de la Florenta au fost publicate in European Neuropsychopharmacoly, 63, 2022, p. e108. (doi: 10.1016/j.euroneuro.2022.07.205).
Atat la sedintta PGC -Bipolar Working Group din 7 septembrie 2022, cat si la sedinta grupului la Congresul Mondial de Genetica Psihiatrica de la Florenta esantionul romanesc de pacienti bipolari (rom4) a fost prezentat ca unul din cele trei esantioane nationale din consortiu cu cele ,mai bune rezultate referitoare la determinarea scorului de risc poligenic bazat pe SNP-uri semnificativ asociate cu boala bipolara determinate prin cartare genomica fina. (vezi figura nr. 1).
Figura nr. 1. Rezultatul esantionului romanesc “rom4”’ la calculul PRS bazat pe scanare si cartare genomica fina (prezentare la o teleconferinta PGC-bipolar group).
Figura nr. 2. Grupul Bipolar al Psychiatric Genetics Consortium la Congresul Mondial de Genetica Psihiatrica, Florenta, Septembrie 2022.
2) Directorul de proiect a primit invitatia de a participa la proiectul COST “EUREKA – IMMUNOPSY” - “European Network for Immunocentric Precision Psychiatry” . Proiectul a fost initiat de prof. dr. Marion Leboyer, INSERM, Paris (vezi invitatia). Proiectele COST sunt proiecte de diseminare de informatie, instruire si initiere de colaborari stiintifice
PARTICIPARI LA MANIFESTARI STIINTIFICE INTERNE SI INTERNATIONALE, 2023
1. Conferinta Nationala de Psihiatrie, Bucuresti , 7-10 iunie 2023
La invitatia presedintei Asociatiei Romane de Psihiatrie, dr. Ana Giurgiuca , trei membri ai echipei au participat cu prezentari orale la Conferinta Nationala de Psihiatrie organizata la Bucuresti in perioada 7-10 iunie 2023
Directorul de proiect a prezentat lucrarea “Ce ar trebui sa stie un psihiatru despre utilizarea clinica a testelor genetice in diagnosticul si tratamentul bolilor psihice”. (vezi program)
Dr. Carmen Diaconu, dr. Ana Iulia Neau si dr. Maria Grigoroiu-Serbanescu au prezentat lucrarea “Efectele pandemiei COVID-19 asupra patologiei psihiatrice in Romania si relația cu structura genetica a populațiilor.”
2. Congresul Mondial de Psihiatrie al Asociatiei Mondiale de Psihiatrie (World Psychiatric Association) (WPA), Viena, 27 septembrie-1 octombrie 2023
La acest congress, in sectita de genetica, directorul de proiect a avut prezentarea orala “Psychosis in bipolar disorder and schizophrenia polygenic risk scores”, autori Maria Grigoroiu-Serbanescu Tracey van der Veen (UK) , Tim Bigdeli (SUA), Stefan Herms (Germania), Carmen C Diaconu, Ana Iulia Neagu, Nick Bass (UK), Markus M. Nöthen (Germania) , Andreas J Forstner (Germania), Andrew McQuillin (UK).
3. Scoala de vara de la Pisa (Italia) , 4-7 septembrie 2023 cu tema “P2X receptors from basic research to market translation” in cadrul proiectului COST “P2X receptors a common route in different diseases: preclinical and clinical aspects” (finantata de Uniunea Europeana). La invitatia Universitatii din Ferrara (Italia) directorul de proiect a tinut prezentarea orala cu tema “P2RX gene in PGC studies of bipolar disorder and unipolar major depression” .
Referinte
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Brainstorm Consortium. Anttila V, Bulik-Sullivan B; Finucane, HK. …. (Grigoroiu-Serbanescu M listed in Bipolar Consortium) (685 authors). Analysis of shared heritability in common disorders of the brain. Science, 2018, 360 (6395), pii: eaap8757;
Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium (Grigoroiu-Serbanescu M listed in Bipolar Disorder Group). Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell, 2018; 173(7):1705-1715.
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Xiao X, Zhang C, Grigoroiu-Serbanescu M (corresponding Author), Wang L, Li L, Zhou D, Yuan TF, Wang C, Chang H, Wu Y, Li Y, Wu DD, Yao YG, Li M. The cAMP responsiveelement-binding (CREB)-1 gene increases risk of major psychiatric disorders. Molecular Psychiatry, 2018 ; 23(9):1-11